Differentiation of immature oligodendrocytes is regulated by phosphorylation of cyclic AMP-response element binding protein by a protein kinase C signaling cascade

Authors

  • Hatsuki Shiga,

    1. Division of Biological Sciences, Graduate School of Science, Hokkaido University, Kita-ku, Sapporo, Japan
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  • Yukako Yamane,

    1. Division of Biological Sciences, Graduate School of Science, Hokkaido University, Kita-ku, Sapporo, Japan
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  • Minoru Kubo,

    1. Division of Biological Sciences, Graduate School of Science, Hokkaido University, Kita-ku, Sapporo, Japan
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  • Yoko Sakurai,

    1. Proteomics Collaboration Research Group, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, Japan
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  • Hiroaki Asou,

    1. Neuronal Function Research Group, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, Japan
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  • Etsuro Ito

    Corresponding author
    1. Division of Biological Sciences, Graduate School of Science, Hokkaido University, Kita-ku, Sapporo, Japan
    2. Division of Innovative Research, Creative Research Initiative “Sousei” (CRIS), Hokkaido University, Kita-ku, Sapporo, Japan
    • Division of Biological Sciences, Graduate School of Science, Hokkaido University, North 10, West 8, Kita-ku, Sapporo 060-0810, Japan
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Abstract

Previous experiments showed that the expression and phosphorylation levels of cyclic AMP-response element binding protein (CREB) are important factors that regulate oligodendrocyte differentiation. The present study was designed to determine whether CREB phosphorylation advances oligodendrocyte differentiation or vice versa and to identify the protein kinase that primarily regulates CREB phosphorylation. We examined the expression and phosphorylation levels of CREB in developing oligodendrocytes at a specific differentiation stage by double-immunocytochemical staining with specific differentiation markers and antibody for phosphorylated CREB. We found that the CREB expression level increased along oligodendrocyte differentiation, and that its phosphorylated level was highest in immature oligodendrocytes. We also showed that CREB phosphorylation was regulated principally by protein kinase C (PKC) activity in immature oligodendrocytes. Our findings suggest that CREB phosphorylation is dependent on a PKC signaling cascade, and this phosphorylation activates CREB-mediated transcription and advances the differentiation of immature to mature oligodendrocytes. © 2005 Wiley-Liss, Inc.

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